On January 30, 2019, ANI Pharmaceuticals, Inc. (the “Company”) entered into Amendment No. 4 to its Asset Purchase Agreement (the “Purchase Agreement Amendment”) with Teva Pharmaceuticals USA, Inc. (“Teva”). Under the terms of the Purchase Agreement Amendment, all royalty obligations of the Company owed to Teva with respect to products associated with ten ANDAs under the Asset Purchase Agreement shall cease effective as of December 31, 2018. In consideration for the termination of such future royalty obligations, the Company agreed to pay Teva a sum of $16,000,000.
Friday, February 1, 2019
Quotient Update on Performance, Disease Screening Field Trial
Quotient Limited (NASDAQ: QTNT) (Quotient or the Company), a commercial-stage diagnostics company, today provided internal performance evaluation data for its extended immunohematology (IH) microarray, and announced the commencement of the European field trial for its initial Serological Disease Screening (SDS) microarray. The Company also disclosed continued strong top line growth in its core liquid reagent business for the quarter and for the nine months ended December 31, 2018.
“I am very pleased to report the progress which we have been able to make. We are well positioned with an ISO certified MosaiQ manufacturing system, a CE marked MosaiQ instrument and the resources required to bring a commercializable MosaiQ testing menu to the transfusion diagnostics market. The Quotient team continues to operate well to achieve the targets which we set earlier this fiscal year.” said Franz Walt, Quotient’s Chief Executive Officer. Mr. Walt added “Our ongoing menu expansion plans are progressing well as evidenced by our first SDS microarray entering its field trial and the development data for our extended antigen panel. When available, the extended antigen panel is designed to be a game changing innovation which will replace the initial IH menu that is planned for use in our European hypercare launch.”
Alkermes briefly falls, rebounds after announcing CRL for ALKS 5461
After the market close on February 1, Alkermes (ALKS) announced it received a Complete Response Letter, or CRL, from the FDA regarding its New Drug Application, or NDA, for ALKS 5461 for the adjunctive treatment of major depressive disorder, or MDD. FDA COMPLETE RESPONSE LETTER: The CRL stated that the FDA was unable to approve the ALKS 5461 NDA in its present form, and was requesting additional clinical data to provide substantial evidence of effectiveness of ALKS 5461 for the adjunctive treatment of MDD. Alkermes said it plans to meet with the FDA to discuss the contents of the CRL and potential next steps for ALKS 5461. This interaction with the FDA will inform whether there is a viable path forward for the ALKS 5461 program. The NDA submission for ALKS 5461 was based on results from a clinical efficacy and safety package with data from more than 30 clinical trials and more than 1,500 patients with MDD. ALKS 5461: ALKS 5461 is a proprietary, investigational, once-daily oral medicine that acts as an opioid system modulator and represents a novel mechanism of action for the adjunctive treatment of MDD, in patients with an inadequate response to standard antidepressant therapies. An estimated 16.2M people in the U.S. suffered from MDD in 2016, the majority of whom may not adequately respond to initial antidepressant therapy. CRL EXPECTED BY ALKERMES CEO: On January 8, Alkermes CEO Richard Pops, during a breakout session at the JPMorgan Healthcare Conference, said his company expected the FDA to issue a Complete Response Letter for its depression candidate ALKS 5461. PRICE ACTION: After initially falling 10% in reaction to the news after-hours, shares of Alkermes are little changed, down 0.2% to $33.08
Alkermes receives CRL from FDA for ALKS 5461 New Drug Application
Alkermes announced that it received a Complete Response Letter from the U.S. Food and Drug Administration regarding its New Drug Application for ALKS 5461 for the adjunctive treatment of major depressive disorder. The CRL states that the FDA is unable to approve the ALKS 5461 NDA in its present form and is requesting additional clinical data to provide substantial evidence of effectiveness of ALKS 5461 for the adjunctive treatment of MDD. Alkermes plans to meet with the FDA to discuss the contents of the CRL and potential next steps for ALKS 5461. This interaction with the Agency will inform whether there is a viable path forward for the ALKS 5461 program. The NDA submission for ALKS 5461 was based on results from a clinical efficacy and safety package with data from more than 30 clinical trials and more than 1,500 patients with MDD. Throughout the clinical development program, ALKS 5461 demonstrated a consistent profile of antidepressant activity, safety and tolerability in the adjunctive treatment of MDD.
Bacteria promote lung tumor development
MIT cancer biologists have discovered a new mechanism that lung tumors exploit to promote their own survival: These tumors alter bacterial populations within the lung, provoking the immune system to create an inflammatory environment that in turn helps the tumor cells to thrive.
In mice that were genetically programmed to develop lung cancer, those raised in a bacteria-free environment developed much smaller tumors than mice raised under normal conditions, the researchers found. Furthermore, the researchers were able to greatly reduce the number and size of the lung tumors by treating the mice with antibiotics or blocking the immune cells stimulated by the bacteria.
The findings suggest several possible strategies for developing new lung cancer treatments, the researchers say.
“This research directly links bacterial burden in the lung to lung cancer development and opens up multiple potential avenues toward lung cancer interception and treatment,” says Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research and the senior author of the paper.
Chengcheng Jin, a Koch Institute postdoc, is the lead author of the study, which appears in the Jan. 31 online edition of Cell.
Linking bacteria and cancer
Lung cancer, the leading cause of cancer-related deaths, kills more than 1 million people worldwide per year. Up to 70 percent of lung cancer patients also suffer complications from bacterial infections of the lung. In this study, the MIT team wanted to see whether there was any link between the bacterial populations found in the lungs and the development of lung tumors.
To explore this potential link, the researchers studied genetically engineered mice that express the oncogene Kras and lack the tumor suppressor gene p53. These mice usually develop a type of lung cancer called adenocarcinoma within several weeks.
Mice (and humans) typically have many harmless bacteria growing in their lungs. However, the MIT team found that in the mice engineered to develop lung tumors, the bacterial populations in their lungs changed dramatically. The overall population grew significantly, but the number of different bacterial species went down. The researchers are not sure exactly how the lung cancers bring about these changes, but they suspect one possibility is that tumors may obstruct the airway and prevent bacteria from being cleared from the lungs.
This bacterial population expansion induced immune cells called gamma delta T cells to proliferate and begin secreting inflammatory molecules called cytokines. These molecules, especially IL-17 and IL-22, create a progrowth, prosurvival environment for the tumor cells. They also stimulate activation of neutrophils, another kind of immune cell that releases proinflammatory chemicals, further enhancing the favorable environment for the tumors.
“You can think of it as a feed-forward loop that forms a vicious cycle to further promote tumor growth,” Jin says. “The developing tumors hijack existing immune cells in the lungs, using them to their own advantage through a mechanism that’s dependent on local bacteria.”
However, in mice that were born and raised in a germ-free environment, this immune reaction did not occur and the tumors the mice developed were much smaller.
Blocking tumor growth
The researchers found that when they treated the mice with antibiotics either two or seven weeks after the tumors began to grow, the tumors shrank by about 50 percent. The tumors also shrank if the researchers gave the mice drugs that block gamma delta T cells or that block IL-17.
The researchers believe that such drugs may be worth testing in humans, because when they analyzed human lung tumors, they found altered bacterial signals similar to those seen in the mice that developed cancer. The human lung tumor samples also had unusually high numbers of gamma delta T cells.
“If we can come up with ways to selectively block the bacteria that are causing all of these effects, or if we can block the cytokines that activate the gamma delta T cells or neutralize their downstream pathogenic factors, these could all be potential new ways to treat lung cancer,” Jin says.
Many such drugs already exist, and the researchers are testing some of them in their mouse model in hopes of eventually testing them in humans. The researchers are also working on determining which strains of bacteria are elevated in lung tumors, so they can try to find antibiotics that would selectively kill those bacteria.
The research was funded, in part, by a Lung Cancer Concept Award from the Department of Defense, a Cancer Center Support (core) grant from the National Cancer Institute, the Howard Hughes Medical Institute, and a Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award.
Story Source:
Materials provided by Massachusetts Institute of Technology. Original written by Anne Trafton. Note: Content may be edited for style and length.
Journal Reference:
- Chengcheng Jin, Georgia K. Lagoudas, Chen Zhao, Susan Bullman, Arjun Bhutkar, Bo Hu, Samuel Ameh, Demi Sandel, Xu Sue Liang, Sarah Mazzilli, Mark T. Whary, Matthew Meyerson, Ronald Germain, Paul C. Blainey, James G. Fox, Tyler Jacks. Commensal Microbiota Promote Lung Cancer Development via γδ T Cells. Cell, Jan. 31, 2019; DOI: 10.1016/j.cell.2018.12.040
Newly discovered gene governs need for sleep when sick
Humans spend nearly one-third of their lives in slumber, yet sleep is still one of biology’s most enduring mysteries. Little is known about what genetic or molecular forces drive the need to sleep — until now. In a study of over 12,000 lines of fruit flies, researchers from the Perelman School of Medicine at the University of Pennsylvania have found a single gene, called nemuri, that increases the need for sleep. These findings are published today in Science.
The NEMURI protein fights germs with its inherent antimicrobial activity and it is secreted by cells in the brain to drive prolonged, deep sleep after an infection.
“While it’s a common notion that sleep and healing are tightly related, our study directly links sleep to the immune system and provides a potential explanation for how sleep increases during sickness,” said senior author Amita Sehgal, PhD, a professor of Neuroscience and director of Penn’s Chronobiology Program.
Without the nemuri gene, flies were more easily aroused during daily sleep, and their acute need for an increase in sleep — induced by sleep deprivation or infection — was reduced. On the other hand, sleep deprivation, which increases the need for sleep, and to some extent infection, stimulated nemuri to be expressed in a small set of fly neurons nestled close to a known sleep-promoting structure in the brain. Overexpression of nemuri increased sleep in bacteria-infected flies and led to their increased survival compared to non-infected control flies.
In response to infection, NEMURI appears to kill microbes, most likely in the peripheral parts of the fruit fly body, and increases sleep through its action in the brain. Several molecules like NEMURI, which is an antimicrobial peptide (AMP), have multiple functions that help combat infection, but its sleep-promoting role may be just as important for host defense, the researchers suggest, given that increased sleep during sickness promotes survival in the flies.
What’s more, the authors note that cytokines such as interleukin-1 (IL-1), an immune cell molecule, are implicated in human sleep. IL-1 can function in the same pathway as AMPs, and it accumulates after prolonged wakefulness and appears to promote sleep. In mammals, cytokines can induce production of AMPs, but AMPS may also affect the expression of cytokines. Given this interwoven relationship, the researchers conclude that NEMURI is a working link between immune function and sleep.
“The NEMURI protein is a genuine driver of keeping sleep on track under conditions of high sleep need like when we’re sick,” said first author Hirofumi Toda, PhD, a postdoctoral fellow in Sehgal’s lab. “In the next phase of our work, we plan to investigate the mechanism by which NEMURI drives sleep.”
Julie Williams and Michael Gulledge, both from Sehgal’s lab, are also co-authors on this paper. This work was funded by the Howard Hughes Medical Institute and the National Institutes of Health (R01GM123783 402).
Story Source:
Materials provided by University of Pennsylvania School of Medicine. Note: Content may be edited for style and length.
Journal Reference:
- Hirofumi Toda, Julie A. Williams, Michael Gulledge, Amita Sehgal. A sleep-inducing gene, nemuri, links sleep and immune function in Drosophila. Science, 2019 DOI: 10.1126/science.aat1650
Subscribe to:
Posts (Atom)